HMPL-453 in Advanced Malignant Mesothelioma

Advanced Malignant Mesothelioma Clinical Trial

Official title:

A Phase II, Single Arm, Multicenter and Open Labelstudy Evaluating the Efficacy, Safety and Pharmacokinetics of HMPL-453 in Patient With Advanced Malignant Mesothelioma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04290325
• Other study ID #: 2019-453-00CH1
• Status: Recruiting
• Phase: Phase 2
• Start date: December 30, 2019
• Est. completion date: March 17, 2023

Study information

• Verified date: June 2020
• Source: Hutchison Medipharma Limited
• Contact: Wenjuan Ding
• Phone: +8602120671806
• Email: Wenjuand[@]hmplglobal.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a phase II, single arm, multicenter and open-label study to evaluate the efficacy, safety and pharmacokinetic of HMPL-453 in patient with advanced Malignant Mesothelioma

Description:

Histologically confirmed patients with advanced malignant mesothelioma that who was failure of the first -line systemic therapy

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 27
• Est. completion date: March 17, 2023
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1.Signed written informed consent;

• 2.18 years of age or older;

• 3.Histologically diagnosed malignant mesothelioma (including pleura, peritoneum, pericardium, and testicular tendon sheath origin, cell type epithelioid, sarcoma-like, or mixed type), and cannot be cured radically;

• 4.Received one to three regimen of prior systemic therapy and then experienced documented radiographic progression or intolerable toxicity;

• 5.Patients agreed to provide tumor tissue for FGF/FGFR testing;

• 6.Measurable disease by RECIST version 1.1 criteria;

• 7.ECOG performance status = 2.;

Exclusion Criteria:

• 1.Previous treatment with any FGFR inhibitor;

• 2.Received systemic anti-cancer therapy within 3 weeks of the first dose of HMPL-453;

• 3.Major surgery within 4 weeks of the first dose of HMPL-453;

• 4.Use of a strong inducer or inhibitor of cytochrome P450 3A4 (CYP3A4) within 1 week of the first dose of HMPL-453;

• 5.Inadequate conditions as indicated by the following laboratory values:

• Absolute neutrophil count (ANC)<1.5 x 109/L

• Hemoglobin < 80 g/L

• Platelet count <80 x 109/L

• 6.Any of the following conditions of liver and kidney insufficiency:

• Total bilirubin > 1.5 x ULN

• AST and ALT > 2.5 x ULN (> 5 x ULN for patients with liver metastases)

• Creatinine clearance of < 50 mL/min as estimated by the Cockcroft-Gault equation

• 7.International normalized ratio (INR) >1.5 or activated partial thromboplastin time (aPTT) >1.5 x ULN;

• 8.Clinical significant liver disease;

• 9.Known human immunodeficiency virus (HIV) infection

• 10.Previous history of retinal detachment;

• 11.Unable to swallow the study drug.

Related Conditions & MeSH terms

• Advanced Malignant Mesothelioma
• Lung Neoplasms
• Mesothelioma

Intervention

Drug:
• HMPL-453
HMPL-453 tablet

Locations

Country	Name	City	State
China	Shanghai Chest Hospital	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Hutchison Medipharma Limited

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (ORR)	Evaluating ORR of HMPL-453 in patient with advanced malignant mesothelioma	measured up to 6 months after the last subject has been enrolled or all subjects have finished their last PFS follow up, whichever comes first
Secondary	Disease control rate (DCR)	Evaluating DCR of HMPL-453 in patient with advanced malignant mesothelioma	measured up to 6 months after the last subject has been enrolled or all subjects have finished their last PFS follow up, whichever comes first
Secondary	12 weeks DCR	Evaluating 12 weeks DCR of HMPL-453 in patient with advanced malignant mesothelioma	measured on 12 weeks
Secondary	Time to Response (TTR)	Evaluating TTR of HMPL-453 in patient who achieved partial response or complete response according to RECIST 1.1 or mRECIST 1.1	measured on 4 weeks
Secondary	Duration of response (DoR)	Evaluating DoR of HMPL-453 in patient from subject first achieve a complete remission, or partial remission to patient PD, or death whichever comes first.	measured on 30 weeks
Secondary	12 weeks PFS	Evaluating 12 weeks PFS rate of HMPL-453 in patient with advanced malignant mesothelioma	measured on 12 weeks
Secondary	Progression free survival (PFS)	Evaluating PFS of HMPL-453 in patient with advanced malignant mesothelioma.	measured on 20 weeks
Secondary	Overall survival (OS)	Evaluating OS of HMPL-453 in patient with advanced malignant mesothelioma	measured on 60weeks
Secondary	Adverse Event (AE) of HMPL-453 monitoring	The safety endpoints include adverse events (AEs) and serious adverse events (SAEs). Reporting of safety, extent of exposure, concomitant medications and discontinuation of study therapy will be based on all subjects who received at least 1 dose of treatment. The adverse events will be registered according to NCI CTCAE 5.0.	Measured from the first dose to within 30 days after the end of treatment.
Secondary	Maximum plasma concentration (Cmax) of HMPL-453	Evaluating Cmax of Continuous dosing of HMPL-453 in patient with advanced malignant	measured on Cycle 1 day 15 and day 16
Secondary	The time to Cmax (Tmax) of HMPL-453	Evaluating Tmax of Continuous dosing of HMPL-453 in patient with advanced malignant	measured on Cycle 1 day 15 and day 16
Secondary	The area under the plasma concentration-time curve (AUC) of HMPL-453	Evaluating AUC from 0 to the time of the last measurable concentration of HMPL-453 in patient with advanced malignant	measured on Cycle 1 day 15 and day 16